GENIC THERAPY, WHAT IS THE

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G E N E T I C T H E R A P Y, W H A T I S
THE REALITY? (17/03/03)
A B BR E V I ATI O N S

NK : Natural Killer
DNA : Desoxyribo Nucleic Acid
CFTR : Name of a protein
AIDS : Acquiered Immune Deficiency Syndrome
SCID-X1 : Severe Combined Immuno Deficiency X1
USA : United States America
AFM : French Association against Myopathies

I. INT RO DU CTI O N

Genic therapy appears like a new fundamental stage in history of the medicine. It is like the
creation of vaccines or the anti-infectious discovery. Directly, it could tackle at the causes of
diseases so far incurable, rather their symptoms.

The sphere of applications of genic therapy is very immense and it is already difficult
estimating importance of these repercussions as far as humane health. It stretches from rare
genetic diseases as far as cancers. Drugs which come from knowledge in medical genetics [1]
weigh several billions of dollars, all over the world. More and more, societies investigate in
genome technologies.

The international competition is intense, France has some important advantages participating
and thus asserting its independence as well in the development of the new therapy for sick people
as in the financial control. Therefore, it need coordinate the actions between research organism,
public hospitals, private companies and associations like AFM.

Accordingly, we can wonder if the genic therapy is a reality? To answer this question, I would
like to developing several aspects. The first part concerns the process of genic therapy, people
concerned by this application and several experiments. Next, I’ll concentrate on advantages and
problems, before to conclude.

ICII. GENIC THERAPY AND ITS
PRO CESS
1. Its principle
Genic therapy need many biomedical process. This consists in correcting or making up for a
dysfunction which provokes a disease. This can be hereditary or acquired. This therapy consists
in introducing a « drug-gene » inside a precise cell in order to :
correct genic disease thanks to the restoration of the deficient gene function
inhibit or activate the synthesis of the deficient protein
provoke the death of cancerous cells thanks to the introduction of « suicide gene »
stimulate the immune response.
Several methods exist, we are going to explain one of them.

First, some patient’s cells are taken (Figure 1.1). Then, the gene is inserted in a attenuated
virus (2), which enters in the cell core and it puts down the gene by intracellular injection (3).This
virus often is a retrovirus because it transfers easier than other viruses its DNA in the treated cell.
Otherwise, « this transport vehicle » is attenuated or modified so that it doesn’t dangerous to
humans. The modified virus is integrated in patient’s cells (4). The gene takes place in the
genome (5). Cells are injected in the guest (6). The defective protein can be produce for example.

1. We take somatic 2. We delete a piece of
T H E R A P Y,
cells on a patient viral genome
What

3. A functional
human gene is put
6. Cells are injected to on the viral genome
the patient

4. Modified virus is put in
touch with the somatic cells
taken
5. The viral genome with
functional gene is put on cellular
genome

Figure 1 : Process of the genic therapy (according to Encarta encyclopaedia)

2. Some beneficiaries

Genic therapy covers a large therapeutic potential. Three main domains can be quoted :
- genetic diseases

- acquired diseases

- vaccines.

However, we hope applications in arterial hypertension, multiple sclerosis…

* Genetic diseases

As far as genetic diseases are concerned, research is moved towards monogenetic diseases
because they are the most accessible as regards research. For example, we can quote Duchenne’s
myopathy (It is a disease which affects muscles : they degenerate. This disease affects only little
boys (1/3500 births) because this transmission concerns the X chromosome.)[2], cystic fibrosis
(This disease is characterized by an excessive mucus secretion which provokes digestive and
respiratory disorders. In fact, it is the CFTR protein which doesn’t assure its function relating to
the water permeability of cells), A or B haemophilia (http://www.hemofiliacat.org.) One
coagulation factor among others doesn’t function ; as a result, the least hurt can be fatal for
them… Genic therapy is a hope for them. The strategy consists in providing the functional gene,
endure, with all the organism’s cells.

As for other diseases, like hypercholesterolemia (where the anormal expressed protein harms
the cell), scientists want to limitate gene expression or stop synthesis of the protein.

* Acquiered diseases

Several acquired diseases are very studied, like cancers, AIDS (Figure 2), hepatitis, diapetes...

The idea is transferring a gene in the tumour or an organ, other hypothesis are considered.

* Vaccines

It is in this field that some prospects relating to genetic engineering in human health seem the
nearest. Vaccination with DNA presents some advantages : vaccine isn’t expensive, stable and it
can be produced in very large numbers. Vaccines would be very interesting in order to counter
epidemics like AIDS or malaria. However, even if the feasibility was proved among mice, they
must demonstrate the innocuousness with us, in the long term.

.3. Transition from animal to human

* CSID - X1

To verify the tolerance and the effectiveness of all pharmaceutical products to human, clinical
essays must be making. This phase is costly and long. Generally, they need ten years for research
and drug marketing. The first essays are realized before 1995, in the USA, but they failed. These
failures didn’t bring information to correct their works.

Thanks to knowledge and technological development like in the field of the molecular genetics, today,
several works are been carried out. Several children affected by a immune disease, like the severe
combined immuno deficiency X1 (SCID - X1) made the experience of genic therapy. This disease affects
1/100 000 little boys. These children suffer from a lack of immunity. It is hereditary and this disease
affects X chromosome. In fact, the c gamma gene doesn’t function. Well, this gene codes a part of a
polypeptid found in interleukins. The latters are applied in the signposting of immune cells. Accordingly,
the diffenciation from progenitor cell to differenciated cells (T and NK) can’t take place. Therefore, their
specific immune system is deficient. They must live in a sterile environment to survive. All bacteria, virus,
or other parasites can provoke a real problem because they can’t develop an immune response.
Consequently, they can die with a simple cold. To remedy to these risks, scientists attempt to counter the
lack of immunity. The only solution was to realize a bone marrow transplant ; nevertheless, it is very
delicate. After many researches and experiments, Professor Fischer, in Paris, applied genic therapy. What a
challenge! Wilco, a German child took part in the test, the October 22nd 2001. This therapy was a success.
Other children participated to this experiment. Unfortunately, after several months, some developped
cancer. It is a great disappointment, but researches go on, thanks to the AFM (Myopathies French
Association) and volunteers. Nevertheless, essays on human are stopped.

Lastly, in London, two babies affected by SCID-X1, are been treating, but we don’t know in the long
term if they will develop cancer or other negative effects, like Wilco.

III. DISCUSSION

Opinions are different between people, thus, we are going to weigh the pros and cons of genic
therapy.

On the one hand, genic therapy is a progress. Wilco demonstrates there is a success, even if we don’t still
know what will be the future. At least, he takes advantage of his life, with his parents. Usually, they died
when they are one year old. Consequently, he is earning several years. Furthermore, he has no treatment at
home, he must only consult to verify the evolution. Otherwise, there is not the problem due to the
conception of a new child in order to he or she gives his or her bone marrow to the oldest sick child (his
or her brother for example). Thus, this ethical question isn’t topical, it’s the reason why genic therapy is a
good point. Moreover, this technique is a hope to numerous diseases (cancer, genetical diseases, aids).
Owing to toxicity and pain given rise to chemotherapy, its aims is to remedy these problems.

On the other hand, when researchers progress, genic therapy creates large emotions in the families who
meet a disease, because they hope his son, for example, would have been outlive him. But, experiments
are long and these progress can be provoke a great bitterness when they lose a family’s member.
Furthermore, omnipresent business is the despair of families who wish that researches will develop to cure
the disease of their child, when he or she is suffering from rare disease. Indeed, when there is a rare
disease, companies refuse to finance researches, because they would lose turnover, as a result an ignorance
on this subject and no therapy. Moreover, genic therapy can be attempted in both germline or somatic
cells, but for ethical reasons therapy in germline cells is forbidden, but we can wonder if a manic couldn’t
lead experiments, in spite of the ley. At last, several children who have undergone genic therapy,
developped cancers. Cancers are better than their ex-disease? …

IV. SUMMARY
To conclude, I reckon there isn’t evolution without failures. Children who have tested genic
therapy are a good experiment for laboratories. Thanks to them, researchers can progress. If they find
a good system in genic therapy, this will be thanks them. Many children could be benefit from this
progress, and they could live in broad daylight, as everybody.

Genic therapy is a logic expansion of genetic technical used in the medical service. This will offer
treatments to genetic sick people. This therapy will cause real modification in the conception of
therapeutic strategies. In the long term, this will lead to a financial diminution. The industrial boom will be
creative and will allow France to assert itself its independence, in this new medical domain.

Owing to all these reasons, I think genic therapy is important. We must to continue studying it.

On the other hand, the procedure is still difficult in practice. Indeed :
-all the mechanisms are not understood

-the virus must conserve his capacity to penetrate inside the core cell, while bringing the repaired
gene
- the cell must be dividing
- gene must be traduced

- all the molecular system must be functional with the principal difficulty to counter all the
recognition system of an other DNA, in the cell.

Moreover, methods of genic therapy are highly complex (concerning A haemophilia for
example)… They can control in vitro system, but it’s different with a in vivo system. Are we allowed
to modify his or her body (somatic therapy) and his or her descendants’ bodies (germinal therapy) too,
which engage directly others’life?

All the scientists agree, we must set limits without bridling research. If we watch out now, the
next generations will need nothing to be afraid of this new world, on the contrary, maybe this will be
matter of a better world than the best worlds.

VI. VOCABULARY

Accordingly : En consequence

Allow (to) : Permettre

As regards : Du point de vue

Assert itself (to) : S’imposer

Attempt : Tenter

Bone Marrow : Moelle osseuse

Cystic fibrosis : Mucoviscidose

Feasibility : Faisabilité

Guest : Hôte
In broad daylight : Au grand jour

Innocuousness : Innucuité

Manic : Fou furieux